Synthesis of a Galactosylated 4‐Hydroxylysine Building Block and Its Incorporation into a Collagen Immunodominant Glycopeptide

Abstract

An analogue of the immunodominant glycopeptide from type II collagen encompassing residues 256–270 has been prepared by substituting β‐D‐galactopyranosyl‐(2S,4R)‐4‐hydroxy‐L‐lysyl (Gal‐4‐Hyl) for β‐D‐galactopyranosyl‐(2S,5R)‐5‐hydroxy‐L‐lysyl (Gal‐5‐Hyl) at position 264. The synthesis of the 4‐hydroxylysine aglycon started from the known (2S,4S)‐4‐hydroxy‐6‐oxo‐1,2‐piperidinedicarboxylate (3) and involved selective ring‐opening of 3, lactone formation, and N‐acylation of the lactone with glycyl esters. The resulting N‐Fmoc‐protected 4‐hydroxylysyl‐glycine dipeptide derivative was galactosylated in high yield to give a building block suitable for solid‐phase peptide synthesis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)